Semiconducting Polymer Nanomaterials For Biomedical Imaging And Cancer Theranostics

Conjugated polymer nanomaterials and dots?CPNs?as fluorescent probes exhibit superior characteristics such as high brightness,fast emission rates,excellent photostability,nonblinking and nontoxic features.These properties make them well-suited to biological imaging applications.Although semiconducting polymer nanomaterials have received much attention,many problems have arisen,such as biofunctionalization,specific labeling,drug/gene delivery,cancer treatment under novel imaging modes,and fingerprint detection.In this doctoral dissertation,we developed a facile strategy covalently links functional polyethylene glycol molecules to polymer dots while simultaneously providing functional groups for bioconjugation.We also demonstrated oxetane-functionalized semiconducting polymer dots for covalent patterning and rapid visualization of latent fingerprints.In addition,we designed a series of multifunctional and multi-structured polymer nanomaterials,and applied them to many fields such as biomedical imaging,drug/gene delivery,and cancer theranostics.The main findings are summarized as follows:1.Biological functionalization:In some functionalization methods,the functional molecules may fall off from the nanoparticles due to the relatively weak non-covalent interactions.To overcome these drawbacks,we developed a cross-linking strategy to covalently link the functional polymer molecules to the Pdots.Besides,crosslinked Pdots showed enhanced colloidal stability,as well as enhanced physical and chemical stability due to their compact crosslinked 3D nano-sized structures.Among various external stimuli,optical stimulus is especially attractive as it can work cleanly and non-invasively,as well as allowing remote biomedical treatment.Here,we describe a light-induced strategy to crosslink functional molecules to Pdots.2.Cell-specific labeling:The usefulness of Pdots in biological applications is strongly dependent on the quality of the surface functionalization to enable specific recognition.The PEGylated and functionalized Pdots exhibited weak non-specific binding and strong specific labeling compared to non-functionalized Pdots.3.Latent fingerprints imaging:We demonstrate oxetane-functionalized semiconducting polymer dots for covalent patterning and rapid visualization of latent fingerprints.In comparison with inorganic nanoparticles,the Pdots exhibit several important advantages:Pdots are much brigthter and have excellent suface properties;Pdots are based on polymers and are thus biocompatible and eco-friendly.The high fluorescence brightness,large stokes shift,and excellent surface properties of the Pdots lead to fingerprint imaging with high sensitivity and resolution.More importantly,the oxetane groups in the Pdots undergo crosslinking reactions induced by a short-time UV irradiation,forming covalently crosslinked 3D polymer network.The resulting fingerprint patterns exhibit unparalleled stability against rigorous treatment,as compared to those by traditional materials that can be easily destroyed.Our study indicates that the Pdots hold great promise for latent fingerprint imaging and fluorescence anti-counterfeiting applications.4.Polymer Nanocavity:We use photocrosslinkable semiconducting polymers and a porogen?small molecule or degradable polymer?to prepare solid nanospheres.After crosslinking the polymer and removing the porogen,this approach yields semiconducting polymer nanospheres with open cavities.Cavity size is tunable and dependent on the nonreactive porogen.In particular,the cavity size reveals that they are promising carriers for delivering biomacromolecules.5.Drug/gene delivery:We demonstrate that the cavity size variation is able to tune the host-guest interactions,as evidenced by F?rster resonance energy transfer.The bright fluorescence and the drug loading/release behaviors enable spatial and temporal monitoring of intracellular release of drug/siRNA molecules.The siRNA delivery efficiency of the polymer nanocavities is much higher than that of solid Pdots and even slightly higher than that of commercial Lipofectamine vectors.6.Tunable near infrared optical properties:We synthesized a highly absorbing near infrared polymer with different molecular weights.The resulting nanoparticles with different sizes show intense tunable absorption from 630 nm to 811 nm.To the best of our knowledge,this is the first time that semiconducting polymer nanoparticles of the same composition have been shown to have size-dependent properties with tunable absorption up to²00 nm.7.Cancer theranostics:The polymer with high persistence length exhibits remarkably high optical absorption with a peak mass extinction coefficient of 81.7 L g^-1 cm^-1.The nanoparticles show efficient NIR-light-harvesting efficiency as well as high non-radiative decay rates,resulting in a high photothermal conversion efficiency?55%?.The polymer nanoparticles serve as a promising photothermal therapy and photoacoustic imaging contrast agent without causing side effects after in vivo photothermal cancer treatment.The three-dimensional photoacoustic images of subcutaneous tumors clearly show that the nanoparticles greatly enhance the photoacoustic signal.